BOB.1 (MRQ-35)

B-cell-specific transcription of octamer-dependent promoters has been shown to require additional coactivators, which functionally interact with Oct1 and/or Oct2 transcription factors. The BOB.1/OBF.1 coactivator was shown to be a critical determinant of octamer-dependent gene transcription in B lymphocytes. Expression of BOB.1/OBF.1 is restricted largely to B lymphocytes. Analyses of BOB.1/OBF.1 expression in a variety of established B cell lines representing different stages of B cell development has suggested a constitutive, B-cell-specific expression pattern. Interestingly, expression of BOB.1/OBF.1 can be induced in T lymphocytes by costimulation with phorbol ester (PMA) and ionomycin. Furthermore, it was demonstrated that BOB.1/OBF.1 transactivation function in T cells is regulated by costimulation-induced phosphorylation of the transactivation domain. Recently, a specific up-regulation of BOB.1/OBF.1 expression in murine germinal center B cells has been demonstrated. Mice deficient for the BOB.1/OBF.1 coactivator showed specific defects, which were largely restricted to late stages of B cell development. The most prominent phenotype was the complete absence of germinal centers in the secondary lymphoid organs of these mice. No gross alteration of antigen-independent B cell development was observed, although the actual number of mature B cells in the spleen was reduced two to fourfold in these mice. Neither rearrangement of immunoglobulin genes nor expression of the μ-heavy chain were measurably affected in these mice. However, consistent with the failure of germinal center development, BOB.1/OBF.1-deficient mice showed a strong reduction in humoral response to both T-cell-dependent antigens. The levels of secondary immunoglogbulin isotypes other than IgM were dramatically reduced. BOB.1 is expressed in germinal center B-cell, mantle B-cells, and plasma cells. Various lymphomas are also positive for this marker including the following: B-Chronic lymphocytic leukemia, mantle cell lymphoma, follicular lymphoma, marginal zone lymphoma, plasmacytoma, Burkitt lymphoma, diffuse large cell lymphoma, diffuse large B-cell lymphoma, T-cell rich B-cell lymphoma, nodular lymphocyte predominant Hodgkin lymphoma, classic Hodgkin lymphoma.